ID | 56950 |
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著者 |
Ohmori, Iori
Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Ouchida, Mamoru
Department of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Kobayashi, Katsuhiro
Jitsumori, Yoshimi
Mori, Akiko
Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Michiue, Hiroyuki
Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Nishiki, Teiichi
Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Ohtsuka, Yoko
Matsui, Hideki
Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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抄録 | Dravet syndrome is an intractable epileptic syndrome beginning in the first year of life. De novo mutations of SCN1A, which encode the Na(v)1.1 neuronal voltage-gated sodium channel, are considered the major cause of Dravet syndrome. In this study, we investigated genetic modifiers of this syndrome. We performed a mutational analysis of all coding exons of CACNA1A in 48 subjects with Dravet syndrome. To assess the effects of CACNA1A variants on the epileptic phenotypes of Dravet syndrome, we compared clinical features in two genotype groups: 1) subjects harboring SCN1A mutations but no CACNA1A variants (n=20) and 2) subjects with SCN1A mutations plus CACNA1A variants (n=20). CACNA1A variants detected in patients were studied using heterologous expression of recombinant human Ca(v)2.1 in HEK 293 cells and whole-cell patch-clamp recording. Nine CACNA1A variants, including six novel ones, were detected in 21 of the 48 subjects (43.8%). Based on the incidence of variants in healthy controls, most of the variants seemed to be common polymorphisms. However, the subjects harboring SCN1A mutations and CACNA1A variants had absence seizures more frequently than the patients with only SCN1A mutations (8/20 vs. 0/20, p=0.002). Moreover, the former group of subjects exhibited earlier onset of seizures and more frequent prolonged seizures before one year of age, compared to the latter group of subjects. The electrophysiological properties of four of the five novel Ca(v)2.1 variants exhibited biophysical changes consistent with gain-of-function. We conclude that CACNA1A variants in some persons with Dravet syndrome may modify the epileptic phenotypes.
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備考 | CACNA1A variants contribute to severity of seizures in Dravet syndrome
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発行日 | 2013-02
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出版物タイトル |
Neurobiology of disease
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巻 | 50巻
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出版者 | Academic Press
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開始ページ | 209
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終了ページ | 217
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ISSN | 09699961
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NCID | AA11645502
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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論文のバージョン | author
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DOI | |
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関連URL | isVersionOf https://doi.org/10.1016/j.nbd.2012.10.016
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Citation | Iori Ohmori, Mamoru Ouchida, Katsuhiro Kobayashi, Yoshimi Jitsumori, Akiko Mori, Hiroyuki Michiue, Teiichi Nishiki, Yoko Ohtsuka, Hideki Matsui, CACNA1A variants may modify the epileptic phenotype of Dravet syndrome, Neurobiology of Disease, Volume 50, 2013, Pages 209-217, ISSN 0969-9961, https://doi.org/10.1016/j.nbd.2012.10.016.
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助成機関名 |
文部科学省
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助成番号 | 21390312
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